My LDL is 400. How clogged are my arteries?

[TLDR: Let's look into whether exceedingly high LDL is problematic using myself as a case study. For more content like this, subscribe to my newsletter.]

“Hi my name’s Sameer and I have an LDL over 400.”

“Hi Sameer!”

No that’s not me at an AA meeting. That’s me introducing myself to a new doctor. Once they get over the shock (these days we’re told to keep LDL “cholesterol” under 100) most doctors take out their pad to write a prescription for statins. When I explain that I have no interest in taking a statin because statins are known to cause diabetes, and diabetes is known to be associated with the things that I’m really afraid of (my asthma coming back, my joint pain/arthritis coming back, dementia, heart disease and cancer) their eyes generally glaze over. Sometimes a doctor will attempt to continue the conversation.

“But I’ve prescribed statins to hundreds of patients!”

“Right,” I respond. “And of those hundreds of patients, how many have come back looking healthier, fitter, with lower blood pressure, lower blood glucose, a1c, fasting insulin and so on?”

At this point the doctor generally opens their mouth makes a little noise and then closes their mouth again.

“And how many went on to gain more weight and then take more and more medications every year including blood pressure medications, metformin, or maybe a blood thinner? And how many went on to get other diagnoses, maybe diabetes, Alzheimers or even cancer?”

At this point the doctor goes quiet. Though they don’t answer my questions, I know that they know the answers. Precisely none of their patients who’ve gone on statins have gone on to become healthier as a result of taking the statin and nearly all of the patients who go on statins go on to develop other problems.

In fairness, not all of the doctors repeat the conversation. My latest consultation with a young doctor was refreshing.

“I understand that you’re in better shape than 99% of my patients, Sameer,” he said. “I agree that you probably don’t need a statin. You’re eating a very healthy meat-based diet, you’re exercising, your blood sugar and fasting insulin are low. You’re doing all the right things. But you have to understand, we’ve never seen markers like this. I would feel a lot better if you at least got a CAC test or something like that so that we have some idea of whether or not you are developing coronary artery disease.”

The point that most doctors have never seen a patient like me is definitely true. The Lean Mass Hyper Responder (LMHR) phenotype which involves the triad - high LDL, high HDL and low triglycerides - is extremely rare in the general public. In the low carb community it feels as though it’s relatively common because this story gets repeated over and over, but it’s not at all common. Even for those doing low carb, most see either no increase or a slight increase in LDL. It’s only about 10% of us who see the LDL go through the roof, for reasons that remain unclear. And it’s hard to estimate how many people have LDL as high as mine in conjunction with high HDL and low triglycerides, but it’s probably less than 0.01% of the general population.

My own view is that regardless of what’s going on at the biological level with the LMHR phenotype, there’s probably no reason for concern. Coronary artery disease is a process that builds up over time and is a response to inflammation. That inflammation can be caused by stress, smoking, or metabolic dysfunction (pre-diabetes and diabetes). It may be the case the high LDL is a problem in a person who's suffering from inflammation (and unfortunately that's most of us living in our toxic food environments). But if there’s no inflammation there’s no reason to think that high LDL is problematic. And low-carb diets are great at reducing inflammation.

There are other reasons not to worry about higher LDL. LDL as a molecule of interest was only identified because people started developing heart disease in the 1950s. There are lots of populations with high LDL eating their culturally appropriate diet that never develop heart disease. I go into this and some other “first principles” here:

That aside, my doctor’s recommendation to look into some further testing - particularly a coronary artery calcium (CAC) test - is a good idea. At best it would be reassuring and at worst it would inform me about any heart disease that I might already have.

By way of background, my LDL has always been on the higher side of normal. Even in my vegan days my LDL was in the 120-130 range, considered high-normal at the time. One reason that I ended up in such bad shape health-wise is that I was concerned about lowering my cholesterol. I would eat foods like oats and beans that are known to reduce cholesterol. My cholesterol would go down, but I was getting sick from all the sugar and plant toxins in these "healthy" foods.

When I got healthy (by doing the opposite of what every health guru and doctor ever told me) my LDL went through the roof. It’s been as high as 470 and currently hovers around 400.

So what would the lipid-heart hypothesis predict in such a case? Following the model advanced by mainstream scientists I respect in this field (Dr. Peter Attia among them), higher lifetime exposure to apoB containing lipoproteins (of which LDL is one) is causally associated with coronary artery disease. Coronary artery disease can begin in an individual’s 20s and accumulates slowly through plaque progression. Plaque progression is dose responsive, meaning the more apoB the greater the plaque progression. Over time the soft plaques become hard plaques which then calcify. The soft plaques are what causes a heart attack, but in some overwhelming percentage of patients (call it 99% for now) those soft plaques are only dangerous when they form on top of older plaques that have hardened (calcified). The new soft plaques on top of the old hard plaques are what usually break off and give someone a heart attack.

So if apoB exposure over a lifetime was causing heart disease, someone like me who’s always had high apoB and for the past 6 years has had astronomically high apoB would expect to see at least some calcified plaque in a CAC score.

In my particular case I was pretty sure I was going to see some calcified plaque. Why? For one thing I used to smoke cigarettes, and that’s a major driver of heart disease. For another my vegan and then vegetarian diet for most of my life was terrible enough to give me all sorts of diseases, including the metabolic syndrome that I now believe is a root cause of heart disease. That got bad enough that I started to have all kinds of symptoms - asthma, arthritis, autoimmune, and more. It may have been giving me heart disease - I do remember some weird heart palpitations I couldn’t explain and never got checked out in my plant-based days. And I have a family history of heart disease, so my genes aren’t doing me any favours.

I went into the test assuming that my score would be higher than zero. The plan would then be to retest in a year to see if my low-inflammation diet was preventing disease progression or if my high LDL was causing progression (as the mainstream would surmise). Once you have a non-zero score, CAC progression is expected to continue at the rate of 10-15% per year; studies show that if you can stop progression, your risk of having a heart attack is as low as those with a zero score.

The way to go into any medical test is with an open mind. I have my bias based on my understanding of the literature, but the literature may be wrong. So, keeping an open mind, there were four possibilities going into this test:

1. High CAC (higher than 300). In this case I would have to do some serious reconsidering. At least I would have to see a cardiologist. I might have to consider going on a statin or some other therapy. There might be tears involved in this scenario and certainly a fair bit of hand-wringing. Retest or do other tests sooner rather than later.

2. Medium CAC (100-300). In this case I might see a cardiologist as well. I’d probably want to get a CT angiogram done which can test for non-calcified plaques to see if I was at high risk for a heart attack or stroke. 

3. Low CAC (0-100). This is the most likely scenario given my previous history. If this is the result, I just assume I’m doing most things right. Retest in a year to monitor disease progression.

4. Zero CAC. This is an unlikely and best case scenario. If it’s a zero, I throw a party.

So with these scenarios in place, I went off to test my CAC. I won’t bore you with the details except to say that it was a fairly inexpensive test ($125 USD) and that I needed a GP referral to get it. I know that in some places it’s cheaper than this and can be done without a GP referral.

The result? A zero score! Woot!

The standard advice is that if you get a zero score, you’re at very low risk of cardiovascular disease for about the next five years. At that point you should repeat the test. Of course very low risk is not zero risk. There are things like stress which can precipitate a cardiovascular event without any other risk factors. A friend of mine had a stroke upon receiving news that her son had been killed in Afghanistan. It’s unlikely that a zero CAC score has any bearing on that kind of cardiovascular event, but I’m extremely unlikely to suffer a heart attack while walking down the street or going to the toilet.

The moment I started talking publicly about this result this the criticisms started coming in.

“Ya but, what about soft plaque?”

“Well you’re still young so we would expect a zero score?”

My response to this is bemusement.

Soft plaque can be measured by a CT angiogram, which is a much more expensive test than the $125 I spent to test my CAC. If my trolls want to start a “Sameer’s CT angiogram fund” I suppose I might consider it. (Please don’t do that, there are plenty of better causes to donate money to.) And CACs are very effective at predicting risk, especially at the level of a zero score.

Secondly, we know from the studies that roughly 30% of people in my age group (I’m 47) will have a CAC of more than zero. If there was any truth at all to the lipid heart hypothesis, wouldn’t we expect someone who’s had high cholesterol his whole life, unbelievably high cholesterol for several years, and even smoked cigarettes to be in the top third when it comes to risk? And if not (and I can already hear the excuses, most using the term "multi-factoral") how useful is the lipid heart hypothesis?

Sadly, I know that none of this is going to change the opinion of the ideologues. They will continue to recommend statins and PCSK9 inhibitors for as long as some company is profiting from those recommendations. They’ve invested too much in this narrative to do otherwise - too much time, too much money and too many reputations.

But this is not about the ideologues. This is about the person who went on a low carb diet, feels great, saw huge improvements in blood markers, a1c, fasting insulin and so on. Maybe that person improved their mental health and is finally learning what it means to live without crippling anxiety or depression or even schizophrenia. What should we tell that person about the one marker that didn’t improve - LDL? Must that high LDL be a cause for concern?

My answer to that is no. If you’re stressed about it, first of all remember that stress does cause heart attacks (no one disputes that). Have faith that your body is no more likely to send you to an early grave than when you were suffering from whatever ailments the low-carb diet helped you to overcome.

Then, if you’re still worried, go out and get a CAC test.

Maybe you have reason to be worried. But chances are you, like me, are doing fine.

As a last thought, consider this question: What would it take to disprove the lipid-heart hypothesis? What level of evidence would be sufficient? There is a wealth of population data showing that higher cholesterol and LDL levels tend to correspond with longer lifespan and longer health span. When I point this out to the zealots they find excuses as to why this might be the case. They make it sound as if the burden of proof is on those of us who think our bodies probably have some good reason for sending our LDL up at times of relative health (to be clear, I feel better physically at age 47 than I did at age 37, 27, or even 17).

But they - the LDL zealots - are the ones who are advancing a hypothesis that is yet to be proven. I and thousands of people like me offer data points that don’t fit their hypothesis. Serious scientists would take those data points seriously and revise their hypothesis. Unfortunately serious scientists are nowhere to be found among the zealots.

At the end of the day, what are we arguing about? Hippocrates, considered the founder of modern medicine, is credited with the following statement: "First, do no harm." What that means is that unless you have evidence that the status quo is harming the patient, you are not allowed to act. Or put another way, your intervention should cause less harm than doing nothing. Statins and PCSK9 inhibitors, like all drugs, have side effects. In other words they can cause harm. Is that harm justifiable? Perhaps. But exposing a patient to those risks without evidence that they're actually suffering from heart disease is negligence. And, as my case and many others clearly document, LDL levels alone cannot serve as a proxy for heart disease progression.